Novel In Vitro and In Vivo Models and Potential New Therapeutics to Break the Vicious Cycle of Cryptosporidium Infection and Malnutrition
Background. Although several animal models of cryptosporidiosis have been reported, most involve genetically or pharmacologically immune-suppressed hosts. Methods. We report challenge with excysted (in vitro and in vivo) and unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenoc...
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| Veröffentlicht in: | The Journal of infectious diseases 2012-05, Vol.205 (9), p.1464-1471 |
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| creator | Costa, Lourrany B. Noronha, Francisco Jose Roche, James K. Sevilleja, Jesus Emmanuel Warren, Cirle A. Oriá, Reinaldo Lima, Aldo Guerrant, Richard L. |
| description | Background. Although several animal models of cryptosporidiosis have been reported, most involve genetically or pharmacologically immune-suppressed hosts. Methods. We report challenge with excysted (in vitro and in vivo) and unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8) cells and weaned nourished and malnourished C57BL/6 mice, following outcomes of growth rate, stool shedding, and tissue burden. We tested treatment with an oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) and alanyl-glutamine in vivo and in vitro. Results. C. parvum—challenged mice showed prolonged weight loss (>10% over 4 days), robust stool shedding (>3 logs/d over 7 days), and epithelial infection in the ileum, cecum, and colon. Of 2 potential therapeutic compounds evaluated in the model, CpG-ODN reduced body weight loss (to |
| doi_str_mv | 10.1093/infdis/jis216 |
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Although several animal models of cryptosporidiosis have been reported, most involve genetically or pharmacologically immune-suppressed hosts. Methods. We report challenge with excysted (in vitro and in vivo) and unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8) cells and weaned nourished and malnourished C57BL/6 mice, following outcomes of growth rate, stool shedding, and tissue burden. We tested treatment with an oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) and alanyl-glutamine in vivo and in vitro. Results. C. parvum—challenged mice showed prolonged weight loss (>10% over 4 days), robust stool shedding (>3 logs/d over 7 days), and epithelial infection in the ileum, cecum, and colon. Of 2 potential therapeutic compounds evaluated in the model, CpG-ODN reduced body weight loss (to <6% on days 3—7 after challenge), reduced shedding of organisms (by 25% on days 1 and 3 after challenge), and decreased the burden of parasites in the ileum. Alanyl-glutamine showed similar benefits. In vitro findings suggested that effects on the epithelial component of the mucosa probably likely responsible for beneficial effects seen in vivo. Conclusions. Weaned mice provide a convenient and reproducible model of cryptosporidial disease, including its vicious cycle with body weight loss and heavier infection with malnutrition, and this model may be useful in exploring innovative therapeutic solutions for this challenging infectious disease.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jis216</identifier><identifier>PMID: 22454464</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animal models ; Animals ; Biological and medical sciences ; Cell Line, Tumor ; Colon - drug effects ; Colon - parasitology ; Colon - pathology ; Cryptosporidiosis ; Cryptosporidiosis - complications ; Cryptosporidiosis - pathology ; Cryptosporidiosis - therapy ; Cryptosporidium parvum - isolation & purification ; Cryptosporidium parvum - pathogenicity ; Dipeptides - therapeutic use ; Disease models ; DNA, Protozoan - genetics ; DNA, Protozoan - isolation & purification ; Feces - parasitology ; Female ; Fundamental and applied biological sciences. Psychology ; Health care administration ; Human protozoal diseases ; Humans ; Ileum ; Ileum - drug effects ; Ileum - parasitology ; Ileum - pathology ; Infections ; Infectious diseases ; Major and Brief Reports ; Malnutrition ; Malnutrition - complications ; Malnutrition - parasitology ; Malnutrition - pathology ; Malnutrition - therapy ; Medical sciences ; Medical treatment ; Mice ; Mice, Inbred C57BL ; Microbiology ; Oligodeoxyribonucleotides - therapeutic use ; Oocysts ; Parasites ; Parasitic diseases ; Protozoal diseases</subject><ispartof>The Journal of infectious diseases, 2012-05, Vol.205 (9), p.1464-1471</ispartof><rights>Copyright © 2012 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>2015 INIST-CNRS</rights><rights>The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-a87b897124db4e204df1b933eb25827af67cd34e8052c562ace11026d8948f1b3</citedby><cites>FETCH-LOGICAL-c504t-a87b897124db4e204df1b933eb25827af67cd34e8052c562ace11026d8948f1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23215993$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23215993$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25836231$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22454464$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa, Lourrany B.</creatorcontrib><creatorcontrib>Noronha, Francisco Jose</creatorcontrib><creatorcontrib>Roche, James K.</creatorcontrib><creatorcontrib>Sevilleja, Jesus Emmanuel</creatorcontrib><creatorcontrib>Warren, Cirle A.</creatorcontrib><creatorcontrib>Oriá, Reinaldo</creatorcontrib><creatorcontrib>Lima, Aldo</creatorcontrib><creatorcontrib>Guerrant, Richard L.</creatorcontrib><title>Novel In Vitro and In Vivo Models and Potential New Therapeutics to Break the Vicious Cycle of Cryptosporidium Infection and Malnutrition</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Background. Although several animal models of cryptosporidiosis have been reported, most involve genetically or pharmacologically immune-suppressed hosts. Methods. We report challenge with excysted (in vitro and in vivo) and unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8) cells and weaned nourished and malnourished C57BL/6 mice, following outcomes of growth rate, stool shedding, and tissue burden. We tested treatment with an oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) and alanyl-glutamine in vivo and in vitro. Results. C. parvum—challenged mice showed prolonged weight loss (>10% over 4 days), robust stool shedding (>3 logs/d over 7 days), and epithelial infection in the ileum, cecum, and colon. Of 2 potential therapeutic compounds evaluated in the model, CpG-ODN reduced body weight loss (to <6% on days 3—7 after challenge), reduced shedding of organisms (by 25% on days 1 and 3 after challenge), and decreased the burden of parasites in the ileum. Alanyl-glutamine showed similar benefits. In vitro findings suggested that effects on the epithelial component of the mucosa probably likely responsible for beneficial effects seen in vivo. Conclusions. Weaned mice provide a convenient and reproducible model of cryptosporidial disease, including its vicious cycle with body weight loss and heavier infection with malnutrition, and this model may be useful in exploring innovative therapeutic solutions for this challenging infectious disease.</description><subject>Animal models</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Colon - drug effects</subject><subject>Colon - parasitology</subject><subject>Colon - pathology</subject><subject>Cryptosporidiosis</subject><subject>Cryptosporidiosis - complications</subject><subject>Cryptosporidiosis - pathology</subject><subject>Cryptosporidiosis - therapy</subject><subject>Cryptosporidium parvum - isolation & purification</subject><subject>Cryptosporidium parvum - pathogenicity</subject><subject>Dipeptides - therapeutic use</subject><subject>Disease models</subject><subject>DNA, Protozoan - genetics</subject><subject>DNA, Protozoan - isolation & purification</subject><subject>Feces - parasitology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Health care administration</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Ileum</subject><subject>Ileum - drug effects</subject><subject>Ileum - parasitology</subject><subject>Ileum - pathology</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Major and Brief Reports</subject><subject>Malnutrition</subject><subject>Malnutrition - complications</subject><subject>Malnutrition - parasitology</subject><subject>Malnutrition - pathology</subject><subject>Malnutrition - therapy</subject><subject>Medical sciences</subject><subject>Medical treatment</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Oligodeoxyribonucleotides - therapeutic use</subject><subject>Oocysts</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Protozoal diseases</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtvEzEUhS1ERUNhyRLkDWI1rV_z2iBBBLRSW1gUtpbHvkMcnPFge4LyE_jXOJ00wMryvd89PtcHoReUnFPS8gs79MbGi7WNjFaP0IKWvC6qivLHaEEIYwVt2vYUPY1xTQgRvKqfoFPGRClEJRbo963fgsNXA_5mU_BYDWa-bD2-8QZcvC998QmGZJXDt_AL360gqBGmZHXEyeP3AdQPnFaQ57T1U8TLnXaAfY-XYTcmH0cfrLHTJmv3oJP1w73sjXLDlILdF56hk165CM8P5xn6-vHD3fKyuP786Wr57rrQJRGpUE3dNW1NmTCdAEaE6WnXcg4dKxtWq76qteECGlIyXVZMaaCUsMo0rWgyys_Q21l3nLoNGJ33CsrJMdiNCjvplZX_dwa7kt_9VnLOhCA0C7w5CAT_c4KY5MZGDc6pAfLusm15S_NPN5ksZlIHH2OA_vgKJXKfnpzTk3N6mX_1r7Uj_RBXBl4fABW1cn1Qg87jR65seMX43uLLmVvH5MPfPme0zPb4H7fXsQM</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Costa, Lourrany B.</creator><creator>Noronha, Francisco Jose</creator><creator>Roche, James K.</creator><creator>Sevilleja, Jesus Emmanuel</creator><creator>Warren, Cirle A.</creator><creator>Oriá, Reinaldo</creator><creator>Lima, Aldo</creator><creator>Guerrant, Richard L.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120501</creationdate><title>Novel In Vitro and In Vivo Models and Potential New Therapeutics to Break the Vicious Cycle of Cryptosporidium Infection and Malnutrition</title><author>Costa, Lourrany B. ; Noronha, Francisco Jose ; Roche, James K. ; Sevilleja, Jesus Emmanuel ; Warren, Cirle A. ; Oriá, Reinaldo ; Lima, Aldo ; Guerrant, Richard L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-a87b897124db4e204df1b933eb25827af67cd34e8052c562ace11026d8948f1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Colon - drug effects</topic><topic>Colon - parasitology</topic><topic>Colon - pathology</topic><topic>Cryptosporidiosis</topic><topic>Cryptosporidiosis - complications</topic><topic>Cryptosporidiosis - pathology</topic><topic>Cryptosporidiosis - therapy</topic><topic>Cryptosporidium parvum - isolation & purification</topic><topic>Cryptosporidium parvum - pathogenicity</topic><topic>Dipeptides - therapeutic use</topic><topic>Disease models</topic><topic>DNA, Protozoan - genetics</topic><topic>DNA, Protozoan - isolation & purification</topic><topic>Feces - parasitology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Health care administration</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Ileum</topic><topic>Ileum - drug effects</topic><topic>Ileum - parasitology</topic><topic>Ileum - pathology</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Major and Brief Reports</topic><topic>Malnutrition</topic><topic>Malnutrition - complications</topic><topic>Malnutrition - parasitology</topic><topic>Malnutrition - pathology</topic><topic>Malnutrition - therapy</topic><topic>Medical sciences</topic><topic>Medical treatment</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiology</topic><topic>Oligodeoxyribonucleotides - therapeutic use</topic><topic>Oocysts</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Protozoal diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Costa, Lourrany B.</creatorcontrib><creatorcontrib>Noronha, Francisco Jose</creatorcontrib><creatorcontrib>Roche, James K.</creatorcontrib><creatorcontrib>Sevilleja, Jesus Emmanuel</creatorcontrib><creatorcontrib>Warren, Cirle A.</creatorcontrib><creatorcontrib>Oriá, Reinaldo</creatorcontrib><creatorcontrib>Lima, Aldo</creatorcontrib><creatorcontrib>Guerrant, Richard L.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costa, Lourrany B.</au><au>Noronha, Francisco Jose</au><au>Roche, James K.</au><au>Sevilleja, Jesus Emmanuel</au><au>Warren, Cirle A.</au><au>Oriá, Reinaldo</au><au>Lima, Aldo</au><au>Guerrant, Richard L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel In Vitro and In Vivo Models and Potential New Therapeutics to Break the Vicious Cycle of Cryptosporidium Infection and Malnutrition</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>205</volume><issue>9</issue><spage>1464</spage><epage>1471</epage><pages>1464-1471</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Background. Although several animal models of cryptosporidiosis have been reported, most involve genetically or pharmacologically immune-suppressed hosts. Methods. We report challenge with excysted (in vitro and in vivo) and unexcysted (in vivo) Cryptosporidium parvum oocysts in human colonic adenocarcinoma (HCT-8) cells and weaned nourished and malnourished C57BL/6 mice, following outcomes of growth rate, stool shedding, and tissue burden. We tested treatment with an oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) and alanyl-glutamine in vivo and in vitro. Results. C. parvum—challenged mice showed prolonged weight loss (>10% over 4 days), robust stool shedding (>3 logs/d over 7 days), and epithelial infection in the ileum, cecum, and colon. Of 2 potential therapeutic compounds evaluated in the model, CpG-ODN reduced body weight loss (to <6% on days 3—7 after challenge), reduced shedding of organisms (by 25% on days 1 and 3 after challenge), and decreased the burden of parasites in the ileum. Alanyl-glutamine showed similar benefits. In vitro findings suggested that effects on the epithelial component of the mucosa probably likely responsible for beneficial effects seen in vivo. Conclusions. Weaned mice provide a convenient and reproducible model of cryptosporidial disease, including its vicious cycle with body weight loss and heavier infection with malnutrition, and this model may be useful in exploring innovative therapeutic solutions for this challenging infectious disease.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22454464</pmid><doi>10.1093/infdis/jis216</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals Biological and medical sciences Cell Line, Tumor Colon - drug effects Colon - parasitology Colon - pathology Cryptosporidiosis Cryptosporidiosis - complications Cryptosporidiosis - pathology Cryptosporidiosis - therapy Cryptosporidium parvum - isolation & purification Cryptosporidium parvum - pathogenicity Dipeptides - therapeutic use Disease models DNA, Protozoan - genetics DNA, Protozoan - isolation & purification Feces - parasitology Female Fundamental and applied biological sciences. Psychology Health care administration Human protozoal diseases Humans Ileum Ileum - drug effects Ileum - parasitology Ileum - pathology Infections Infectious diseases Major and Brief Reports Malnutrition Malnutrition - complications Malnutrition - parasitology Malnutrition - pathology Malnutrition - therapy Medical sciences Medical treatment Mice Mice, Inbred C57BL Microbiology Oligodeoxyribonucleotides - therapeutic use Oocysts Parasites Parasitic diseases Protozoal diseases |
| title | Novel In Vitro and In Vivo Models and Potential New Therapeutics to Break the Vicious Cycle of Cryptosporidium Infection and Malnutrition |
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